Data published by researchers at the University of Chicago (Monto et al. (1987) J. Infect. Disease 156, 43 (see Table 2 in the exemplification), has previously shown that RV infection complications increase with age, with lower respiratory tract problems increasing considerably in the 40 or over age group reflected by increased physician consultation. Other studies have also indicated that elderly people, e.g. in care, are more susceptible to severe illness and mortality through RV infection than younger population groups (Louie et al. (2005) Clin. Infect. Dis. 41, 262-265; Falsey et al. (2002) J. Infect. Dis. 185, 1338-1341). This is consistent with decline in innate immunity in the elderly, and with poorer responses to flu vaccinations. Smokers have also been shown to be more susceptible to respiratory tract infections and to the prolonged effects of virus infections such as RV infections (Cohen et al. (1993) ibid; Benseñor et al. (2001) AEP 11, 225-231; Venarske et al. (2006) J. Infect Dis. 193, 1536-1543). Individuals with chronic underlying illnesses such as congestive heart failure are also highly susceptible to the effects of RV infections (El-Sahly et al. (2000) Clin Infect Dis. 31, 96-100).
While IFN-β has previously been known to have anti-viral activity, including in relation to RV infection in in vitro cellular studies and in clinical trials with purposely RV-infected individuals, up to now it has only been proposed, however, for clinical use in relation to RV infection in the context of RV-exacerbation of asthma and chronic obstructive pulmonary disease (COPD). In asthmatics and COPD sufferers, it has been found that there is deficiency of IFN-β production in bronchial epithelial cells in response to RV infection and airway delivery of IFN-β in such patients is thus indicated to prevent or treat RV infection which may otherwise cause severe exacerbation of asthma or COPD (see published International Application WO 2005/087253 and Wark et al. (2005) “Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus” J. Exp. Med. 201, 937-947).
IFN-λ production has also been shown to be deficient in bronchial epithelial cells of asthmatics when challenged with RV infection (published International Application WO 2007/029041). Expression of type I IFN-α/βs and type III IFN-λs are induced in response to known inducers (e.g. viral RNA/DNA, LPS) suggesting overlapping signalling mechanisms leading to their expression (Ank et al. (2006) “Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and by IFNs such as IFNβ and displays potent antiviral activity against select virus infections in vivo” J. Virol. 80, 4501 and Uzé et al. (2007) “IL-28 and IL-29: Newcomers to the IFN family” Biochimie epub ahead of print xx, 1-6). Although IFN-λs bind to a different receptor than that for Type I interferons, the interferon responsive genes and the antiviral response triggered by these two classes of interferons appear to be equivalent (Ank et al (2006) ibid). Hence, IFN-λ has also been proposed for treating viral exacerbation of asthma and COPD, especially, for example, such exacerbation by RV and influenza infection (see published International Application WO 2007/029041 and Contoli et al. (2006) “Role of deficient type III interferon-λ production in asthma exacerbations” Nat Med. 12, 1023-1026).
In contrast, use of IFN-β in individuals with RV infection but who are otherwise healthy has been thought to have no true experimental support. Although the first clinical trial using IFNβ-ser against experimental rhinovirus infection showed promising beneficial results (Higgins et al. (1986) “Interferon-beta ser as prophylaxis against experimental rhinovirus infection in volunteers” J. Interferon Res. 6, 153-159), in a subsequent trial for prophylaxis of natural colds by intranasal delivery, IFNβ-ser was found to be ineffective (Sperber et al. (1989) “Ineffectiveness of recombinant interferon-beta serine nasal drops for prophylaxis of natural colds” J. Infect. Dis. 160, 700-705). This may be accounted for by the innate capacity of RV-infected cells to produce IFN-β in response to such infection.
Evidence is now presented indicating however that such innate capacity is compromised in elderly people, especially long-term smokers. Unexpectedly, and more particularly, cultured bronchial epithelial cells from such smokers have been found to exhibit increased RV-induced cytotoxicity and IFN-β has been shown to protect against such cytotoxic cell death. Hence, clinical utility for airway delivery of IFN-β in elderly people with RV infection, whether or not smokers, whether or not asthmatic or suffering from COPD, is now indicated. Such utility is also extrapolated to IFN-λ.